Vol 6 No 7 July 2010
Though the use of stem cells in research is gradually gaining grounds, it still remains one of the most controversial topics in the medical world. Stem cell debate revolves around the use of Embryonic Stem Cells (ESCs) that involves the creation, usage and destruction of human embryos. Dr Asma Mohd Yousuf presents the views of some experts.
ESCs, being pluripotent, have the ability to evolve into any type of body cell. However, their tremendous potential for uncontrolled growth as well as the use of human embryos as their source of origin has made their use very contentious. Yet, there are some who believe that not using such potentially viable cells in therapy would drastically cut down on the chances of treating some of the existing incurable diseases. Besides, the unused embryos from In Vitro Fertilisation (IVF), even those obtained after abortion can be used to obtain ESCsfor research purposes as these embryos belong to various gestational periods.
Dr B S Rajput Consultant Joint Replacement and Stem Cell Transplant Surgeon, Breach Candy Hospital, Mumbai
The use of ESC in India for research and therapy has been banned by the Indian Council of Medical Research (ICMR). These cells have tremendous potential for growth, albeit uncontrolled. Besides, while treating one disease, these cells can lead to other medical problems. Therefore, the use of ASCs should always be preferred over ESCs as ASCs have controlled and targeted action.
When it comes to exploiting the embryos obtained from abortion cases or those unused embryos acquired from IVF, such embryos should be preserved only for research purposes and organogenesis. They should not be utilised in Stem Cell therapy (SCT).
The US Food and Drug administration (USFDA) had approved the phase-I clinical trials for transplantation of a human-ES-derived cell population into spinal cord-injured individuals. However, their status on Stem Cell Research (SCR) is way behind the rest of world due the prolonged ban on the use of ESCs for research purposes during the Bush regimen. Hence, the use of ESCs in spinal cord injuries trials there is quite primitive.
Today, we are already using advanced technology with allogenic MSCs and gaining satisfactory to appreciable results in cases of spinal cord injuries. SCT is going to evolve into a mainstream therapy in the next decade, as it has already given astonishing results in intractable problems like Duchenne muscular dystrophy, diabetes mellitus, chronic nephropathy and dilated cardiomyopathy, especially post myocardial infarction. When cheaper and safer options are available, it is only wise to opt for them
Dr Ganapathi M BhatConsultant Medical Oncologist & Stem Cell Transplant Physician, Jaslok Hospital & Research Centre, Mumbai
In contrast to countries with strict regulations, in our country foetal stem cells from Medically Terminated Pregnancy (MTP) or from spare embryos generated from IVF clinics are legally approved for use in research and therapy. However, unscrupulous practices by the medical fraternity, to generate embryos must be abandoned.
Our knowledge remains fairly incomplete when it comes to the use of ESCs in human trials. Injudicious use of these cells could lead to formation of tumours (shown in animal studies) hampering further avenues for authentic research. Standards for scientific and ethical excellence are required to be established in tandem with governmental agencies.
Also, it becomes mandatory to ensure that stem cell based treatment is standardised and remains confined to a few, carefully selected, major research hospitals. At the same time, they should be strictly controlled and monitored. The patients should be followed up over a long period and the findings (positive and negative) should be published in indexed medical journals.
Dr Geeta Shroff Medical Director, Nutech Mediworld, New Delhi
There are many Indian organisations that have made progress in stem cell science and brought India to a position of strength in this field. Nutech Mediworld, so far, has treated about 200 cases of chronic spinal cord injury using hESC transplantation. Our proprietary cell culture methodology has led to the creation of hESC lines from a single, spare, throwaway, pre-implantation stage embryo from a natural IVF cycle with full consent. Here, the embryo used is not implanted, and hence, no abortion takes place.
Though the FDA has withdrawn its approval on the world’s first clinical trial using hESC on spinal injury patients due to the adverse effects observed in pre-clinical studies, support for hESC research and therapy by industry, regulators, and the government is a must, as it has the potential of heralding a new era in medicine.
Dr Jyothsna A RaoResearch Director, International Stemcell Services Ltd, Bengaluru
ESCs are omnipotent capable of giving rise to an entire organ. Therefore, their use in SCR is essential. However, it is still too premature to talk about the use of these cells in SCT. The genomes of these cells are extremely plastic and the immunologic rejection of these cells by the body is another matter of concern. Further, when there is a strong scientific evidence for using ASCs for a variety of clinical conditions, then such therapies should be supported, as they offer a safe alternative when compared to ESCs.
The embryos obtained during abortions are used to gain embryonic cells but this practice has to be regulated as abortions could also be induced for gain in some cases. Even when we consider the use of unused embryos from IVF, the effect of this therapy still remains to be seen, especially as the immunological barrier will not allow successful clinical utilisation of these cells.
In India, government grants must support the basic research to probe various facets of the ESCs, as it will help in predicting the fate of this technology in-vivo. But refraining from ESCs driven clinical trials would be suggestive as they predispose the patient to a number of unknown clinical conditions.
Dr Samuel JK AbrahamDirector-NCRM (India) and Cardiac Surgeon, Yamanashi University (Japan)
The research on ESCs should be supported because the ESCs formed from the fusion of two individual cells – sperm and ovum – in the womb become a full-fledged human being with 220 plus differentiated cell types with complex functions. This takes place by coordination of trillions of signals, mechanisms and pathways that are yet to be explored by extensive research. However, its usage for routine treatment is a far cry as of now.
ESCs are considered to be less antigenic; therefore, lesser rejection occurs when administered in a non-autologous manner. They also have excellent potentials for in vitro culture expansion. This makes ESCs the ideal source for stem cells to be made into an off-shelf drug.
However, stem cells cannot be considered as drugs by the regulatory bodies because for a drug, the manufacturing process remains the same at any place of manufacture based on Good Manufaacturing Practice (GMP) standards, whereas stem cell production differs depending upon the tissue, age of the donor and type of stem cell. Also, the route of absorption and excretion as well as the bioavailability of drugs are known, whereas that of stem cells is not entirely identified. Besides, drugs have an antidote but stem cells once injected in the body cannot be traced or neutralised with an antidote.
The purity and tumourigenesis have been major reasons of concerns while deciding the use of ESCs in SCR or SCT. It is due to the tumourigenic property of ESCs that the trial which was started by Geron Corporation, which had initially received the USFDA approval, has been temporarily stopped now. Thus, the research using ESCs in laboratories should be totally supported, but they cannot be used in treatment until the safety and efficacy parameters are proven.
Dr Satish Totey Founder and CEO, Advanced Neuro-Science Allies Pvt Ltd, Bengaluru
Gene expression in stem cells derived from various tissue sources suggests that in stem cells, tissue heterogeneity is biologically relevant. Thus, different tissue sources may generate stem cell products withdifferent cytokine expression profile. Though some ASCs have proved to be effective for few diseases, ESCs have yet to be proven for SCT. Only time will tell how ESCs will be effectively used in therapy.
Unused embryos from IVF procedures should be allowed for obtaining ESCs as they will be anyway discarded if not used. Currently, we do not have embryonic stem cell line that can be used for clinical purpose. Derivation of clinically eligible embryonic stem cell lines is extremely difficult and normal research institute is not equipped for this purpose. Commercial companies should be supported for this purpose.
Embryos from abortion are mostly foetal tissue derived cells and they are not real ESCs. The aborted foetal tissue derived stem cells may be used only after their safety and efficacy has been ascertained. Since these tissues are very close to ESCs, there is always a risk of teratoma formation on transplantation. However, it needs to be ascertained whether these stem cells can form teratoma or not.
We need to take a balanced approach while discussing the pros and cons of stem cells as their use is a ray of hope for incurable diseases. There should be a collective approach in India, in order to hasten the progress of such trials and therapies with emphasis on safety of the patients by strictly adhering to the regulatory guidelines.